2,7-Naphthalenedisulfonic acid, 3-[(1E)-2-[4-[(1E)-2-[4-[(1E)-2-[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]diazenyl]-2-sulfophenyl]diazenyl]-2,5-bis(2-hydroxyethoxy)phenyl]diazenyl]-4,5-dihydroxy-, potassium sodium salt (1:2:1)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria for classification as Reliable without restriction according to Klimisch et al (1997)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

458-890-5

EC Name:

-

Cas Number:

2138848-94-7

Molecular formula:

C35H31N8O18S3.xNa.yK, where x+y=3

IUPAC Name:

dipotassium sodium 3-[(1E)-2-{4-[(1E)-2-{4-[(1E)-2-(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazen-1-yl]-2-sulfonatophenyl}diazen-1-yl]-2,5-bis(2-hydroxyethoxy)phenyl}diazen-1-yl]-4,5-dihydroxynaphthalene-2,7-disulfonate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Method of administration:
Gavage

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

7 days/week

No. of animals per sex per dose:

Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Male: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Mortality: There were no deaths during the study period.

Clinical observations : There were no toxicologically
significant findings.

Behavioural assessment: No treatment-related behavioural
differences were detected.

Functional Performance tests: There wer no treatment-related
changes in sensory reactivity.

bOdyweight: No adverse effect on bodyweight development was
detected.

Food consumption; There was no treatment- related effect on
food consumption or on food efficiency during the study.

Water consumption: Daily visual inspection of the water
bottles revealed no intergroup differences.

Laboratory findings:
Haematology : No treatment-related effects were detected.


Blood chemistry: No treatment related effects were detected.

Effects in organs:
Organ weights: No toxicologically significant effects were
detected in the parameters measured.

Necropsy: No macroscopic abnormalities were detected.

Histopathology: Tubular basophilia/ degeneration was
observed in the kidneys in relatio to treatment for the
female rats dosed at 1000 and 150 mg/kg/day

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

2

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male

3

Dose descriptor:

NOEL

Effect level:

15 mg/kg bw/day (nominal)

Sex:

female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Classified as: Not classified